The cause of systemic lupus erythematosus (SLE) is probably a chronic virus infection occurring in genetically predisposed individuals. A variety of attempts have failed to implicate specific viruses, but recent work suggests enhanced expression of type C oncornavirus antigens in SLE. This is a further parallel to the New Zealand mouse disease model for SLE, where type C antigen expression is markedly increased and where an endogenous virus can be regularly isolated. This project has attempted type C virus isolation from SLE patients for the past 1-1/2 years. SLE cell cultures were cocultivated and fused with other possibly permissive cell lines; chemical induction and long-term subculturing were done. For virus detection, density separation of radiolabelled virus was used first, with negative results on 8 patients. Subsequently, the type C viral RNA-directed DNA polymerase has been used with probably negative results to date on 19 patients. Thus the replication of endogenous type C virus is probably restricted in SLE, as is generally the case in man. This project will attempt virus isolation using methods previously successful in man and other species, combined with novel approaches. After chemical induction, fusion of SLE and various other cells will be done, followed by prolonged subculturing. For virus detection, the method of RNA-directed DNA polymerase will be used. BIBLIOGRAPHIC REFERENCES: Phillips P.E.: Viruses and autoimmunity, in 1975 Yearbook of Science and Technology, ed. D.N. Lapedes (McGraw-Hill, N.Y.) 239-241, 1975. Phillips P.E.: The role of viruses in systemic lupus erythematosus, in Clinics in Rheumatic Disease, Systemic Lupus Erythematosus, ed. NF Rothfield (Saunders, London) 1: 505-518, 1975.